The early morphological and biochemical effects of intrarectally administered 1,2-dimethylhydrazine dihydrochloride on mouse colon were studied. Using [3H]thymidine autoradiography, it was found that 1,2-dimethylhydrazine dihydrochloride, 250 mg/kg decreased the number of prelabeled DNA-synthesizing cells in the distal colon as early as 30 min after instillation. During the interval from 24 hr to 2 weeks, however, the opposite effect was seen; incorporation of [3H]thymidine increased 3- to 5-fold over controls. At lower doses (0.25 to 25 mg/kg), a similar trend was observed. Histological examination showed no dramatic changes in cell structure or in tissue architecture. No changes were seen in labeling indices in the proximal colon. In the liver, cellular alterations were seen at concentrations of 25 to 250 mg/kg, particularly in the centrolobular region. These changes were evident at 2 hr and disappeared by 4 hr. The kidney was unaffected by 1,2-dimethylhydrazine dihydrochloride at any concentration.

Our results suggest that enzymes capable of activating 1,2-dimethylhydrazine dihydrochloride are located within the mucosal cells of the distal colon.

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This investigation was supported by USPHS Research Grants CA-12376 from the National Cancer Institute and CA-15400 through the National Large Bowel Cancer Project.

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